Genome-wide transcription factor-binding maps reveal cell-specific changes in the regulatory architecture of human HSPCs.

Autor:	Subramanian S; School of Clinical Medicine, University of New South Wales, Sydney, Australia., Thoms JAI; School of Biomedical Sciences, University of New South Wales, Sydney, Australia., Huang Y; Centre for Health Technologies and the School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia., Cornejo-Páramo P; Victor Chang Cardiac Research Institute, Sydney, Australia., Koch FC; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, Australia., Jacquelin S; Macrophage Biology Laboratory, Mater Research, Brisbane, Australia., Shen S; Bone Marrow Transplant Laboratory, NSW Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia., Song E; Bone Marrow Transplant Laboratory, NSW Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia., Joshi S; School of Clinical Medicine, University of New South Wales, Sydney, Australia., Brownlee C; Mark Wainwright Analytical Centre, University of New South Wales, Sydney, Australia., Woll PS; Department of Medicine, Center for Hematology and Regenerative Medicine, Karolinska Institutet, Huddinge, Sweden., Chacon-Fajardo D; Centre for Health Technologies and the School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia., Beck D; Centre for Health Technologies and the School of Biomedical Engineering, University of Technology Sydney, Sydney, Australia., Curtis DJ; Australian Centre for Blood Diseases, Monash University, Melbourne, VIC, Australia., Yehson K; Blood Transplant and Cell Therapies Laboratory, NSW Health Pathology, Westmead, NSW, Australia., Antonenas V; Blood Transplant and Cell Therapies Laboratory, NSW Health Pathology, Westmead, NSW, Australia., O'Brien T; Sydney Children's Hospital, Sydney, Australia., Trickett A; Bone Marrow Transplant Laboratory, NSW Health Pathology, Prince of Wales Hospital, Randwick, NSW, Australia., Powell JA; Centre for Cancer Biology, SA Pathology, University of South Australia, Adelaide, Australia.; Adelaide Medical School, The University of Adelaide, Adelaide, Australia., Lewis ID; Centre for Cancer Biology, SA Pathology, University of South Australia, Adelaide, Australia., Pitson SM; Centre for Cancer Biology, SA Pathology, University of South Australia, Adelaide, Australia., Gandhi MK; Blood Cancer Research Group, Mater Research, The University of Queensland, Brisbane, QLD, Australia., Lane SW; Cancer Program, QIMR Berghofer Medical Research, Brisbane, Australia., Vafaee F; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, Australia.; UNSW Data Science Hub, University of New South Wales, Sydney, Australia., Wong ES; Victor Chang Cardiac Research Institute, Sydney, Australia.; School of Biotechnology and Biomolecular Sciences, Faculty of Science, University of New South Wales, Sydney, Australia., Göttgens B; Wellcome-MRC Cambridge Stem Cell Institute, Cambridge, United Kingdom., Alinejad-Rokny H; BioMedical Machine Learning Lab, Graduate School of Biomedical Engineering, University of New South Wales, Sydney, Australia., Wong JWH; School of Biomedical Sciences, Li Ka Shing Faculty of Medicine, The University of Hong Kong, Hong Kong SAR, China., Pimanda JE; School of Clinical Medicine, University of New South Wales, Sydney, Australia.; School of Biomedical Sciences, University of New South Wales, Sydney, Australia.; Haematology Department, Prince of Wales Hospital, Sydney, Australia.
Jazyk:	angličtina
Zdroj:	Blood [Blood] 2023 Oct 26; Vol. 142 (17), pp. 1448-1462.
DOI:	10.1182/blood.2023021120
Abstrakt:	Hematopoietic stem and progenitor cells (HSPCs) rely on a complex interplay among transcription factors (TFs) to regulate differentiation into mature blood cells. A heptad of TFs (FLI1, ERG, GATA2, RUNX1, TAL1, LYL1, LMO2) bind regulatory elements in bulk CD34+ HSPCs. However, whether specific heptad-TF combinations have distinct roles in regulating hematopoietic differentiation remains unknown. We mapped genome-wide chromatin contacts (HiC, H3K27ac, HiChIP), chromatin modifications (H3K4me3, H3K27ac, H3K27me3) and 10 TF binding profiles (heptad, PU.1, CTCF, STAG2) in HSPC subsets (stem/multipotent progenitors plus common myeloid, granulocyte macrophage, and megakaryocyte erythrocyte progenitors) and found TF occupancy and enhancer-promoter interactions varied significantly across cell types and were associated with cell-type-specific gene expression. Distinct regulatory elements were enriched with specific heptad-TF combinations, including stem-cell-specific elements with ERG, and myeloid- and erythroid-specific elements with combinations of FLI1, RUNX1, GATA2, TAL1, LYL1, and LMO2. Furthermore, heptad-occupied regions in HSPCs were subsequently bound by lineage-defining TFs, including PU.1 and GATA1, suggesting that heptad factors may prime regulatory elements for use in mature cell types. We also found that enhancers with cell-type-specific heptad occupancy shared a common grammar with respect to TF binding motifs, suggesting that combinatorial binding of TF complexes was at least partially regulated by features encoded in DNA sequence motifs. Taken together, this study comprehensively characterizes the gene regulatory landscape in rare subpopulations of human HSPCs. The accompanying data sets should serve as a valuable resource for understanding adult hematopoiesis and a framework for analyzing aberrant regulatory networks in leukemic cells. (© 2023 by The American Society of Hematology. Licensed under Creative Commons Attribution-NonCommercial-NoDerivatives 4.0 International (CC BY-NC-ND 4.0), permitting only noncommercial, nonderivative use with attribution. All other rights reserved.)
Databáze:	MEDLINE
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